Chemistry
- A macrolide antibiotic produced from Streptomyceserythreus,
erythromycin is a weak base that is available commercially in several
salts and esters. It has a pKa of
8.9.

Erythromycin base
occurs as a bitter-tasting, odorless or practically odorless, white to
slight yellow, crystalline powder. Approximately 1 mg is soluble in 1 ml
of water; it is soluble in alcohol.

Erythromycin estolate
occurs as a practically tasteless and odorless, white, crystalline powder.
It is practically insoluble in water and approximately 50 mg are soluble
in 1 ml of alcohol. Erythromycin estolate may also be known as
erythromycin propionate lauryl sulfate.

Erythromycin
ethylsuccinate occurs as a practically tasteless and odorless, white to
slight yellow, crystalline powder. It is very slightly soluble in water
and freely soluble in alcohol.

Erythromycin
lactobionate occurs as white to slightly yellow crystals or powder. It may
have a faint odor and is freely soluble in water and alcohol. Erythromycin
gluceptate occurs as a practically odorless, white, slightly hygroscopic
powder that is freely soluble in water and alcohol. It may also be known
as erythromycin glucoheptonate.

Storage/Stability/Compatibility
- Erythromycin (base) capsules and tablets should be stored in tight
containers at room temperature (15-30°C). Erythromycin estolate
preparations should be protected from light. To retain palatability, the
oral suspensions should be refrigerated.

Erythromycin
ethylsuccinate tablets and powder for oral suspension should be stored in
tight containers at room temperature. The commercially available oral
suspension should be stored in the refrigerator to preserve palatability.
After dispensing, the oral suspensions are stable for at least 14 days at
room temperature, but individual products may have longer labeled
stabilities.

Erythromycin
lactobionate powder for injection should be stored at room temperature.
For initial reconstitution (vials), only sterile water for injection
should be used. After reconstitution, the drug is stable for 24 hours at
room temperature and 2 weeks if refrigerated. To prepare for
administration via continuous or intermittent infusion, the drug is
further diluted in 0.9% sodium chloride, Lactated Ringer’s, or
Normosol-R. Other infusion solutions may be used, but first must be
buffered with 4% sodium bicarbonate injection (1 ml per 100 ml of
solution). At pH’s of <5.5, the drug is unstable and loses potency
rapidly. Many drugs are physically incompatible with erythromycin
lactobionate; refer to an appropriate reference (e.g., Trissell—see
bibliography) for more information.

Erythromycin
gluceptate powder for injection should be stored at room temperature. For
initial reconstitution (vials), only sterile water for injection (without
preservatives) should be used. After reconstitution, the drug is stable
for 7 days if refrigerated. Many drugs are physically incompatible with
erythromycin gluceptate; refer to an appropriate reference (e.g.,
Trissell—see bibliography) for more information.

Pharmacology
- Erythromycin is usually a bacteriostatic agent, but in high
concentrations or against highly susceptible organisms it may be
bactericidal. The macrolides (erythromycin and tylosin) are believed to
act by binding to the 50S ribosomal subunit of susceptible bacteria,
thereby inhibiting peptide bond formation.

Erythromycin is less
active at low pH’s and many clinicians suggest alkalinizing the urine if
using the drug to treat UTI’s.

Uses/Indications
-
Erythromycin is approved for use to treat infections caused by
susceptible organisms in dogs, cats, swine, sheep, and cattle. It is
often employed when an animal is hypersensitive to penicillins or if
other antibiotics are ineffective against a certain organism.

Erythromycin is at the
present time considered to be the treatment of choice (with rifampin) for
the treatment of C. (Rhodococcus) equi infections in foals.

Pharmacokinetics
- Erythromycin is absorbed after oral administration in the upper small
intestine. Several factors can influence the bioavailability of
erythromycin, including salt form, dosage form, GI acidity, food in the
stomach, and stomach emptying time. Both erythromycin base and stearate
are susceptible to acid degradation, and enteric coatings are often used
to alleviate this. Both the ethylsuccinate and estolate forms are
dissociated in the upper small intestine and then absorbed. After IM or SQ
injection of the polyethylene-based veterinary product (Erythro®-200;
Gallimycin®-200)
in cattle, absorption is very slow. Bioavailabilities are only about 40%
after SQ injection, and 65% after IM injection.

Erythromycin is
distributed throughout the body into most fluids and tissues including the
prostate, macrophages, and leukocytes. CSF levels are poor. Erythromycin
may be 73-81% bound to serum proteins and the estolate salt, 96% bound.
Erythromycin will cross the placenta and levels of 5-20% of those in the
mother’s serum can be found in the fetal circulation. Erythromycin levels
of about 50% of those found in the serum can be detected in milk. The
volume of distribution for erythromycin in dogs is reportedly 2 L/kg, 3.7
- 7.2 L/kg in foals, 2.3 L/kg in mares, and 0.8 L/kg in cattle.

Erythromycin is
primarily excreted unchanged in the bile, but is also partly metabolized
by the liver via N-demethylation to inactive metabolites. Some of
the drug is reabsorbed after biliary excretion. Only about 2-5% of a dose
is excreted unchanged in the urine. The reported elimination half-life of
erythromycin in various species are: 60-90 minutes in dogs and cats, 60-70
minutes in foals and mares, and 190 minutes in cattle.

Contraindications/Precautions/Reproductive Safety
- Erythromycin is contraindicated in patients hypersensitive to it. In
humans, the estolate form has been associated rarely with the development
of cholestatic hepatitis. This effect has not apparently been reported in
veterinary species, but the estolate should probably be avoided in
patients with preexisting liver dysfunction.

Many clinicians
believe that erythromycin is contraindicated in adult horses (see Adverse
Effects below), and oral erythromycin should not be used in ruminants as
severe diarrheas may result.

While erythromycin has
not demonstrated teratogenic effects in rats and the drug is not thought
to posses serious teratogenic potential, it should only be used during
pregnancy when the benefits outweigh the risks.

Adverse
Effects/Warnings
- Adverse effects are relatively infrequent with erythromycin when used in
small animals, swine, sheep, or cattle. When injected IM, local reactions
and pain at the injection site may occur. Oral erythromycin may cause GI
disturbances with diarrhea, anorexia, and vomiting occasionally seen.
Rectal edema and partial anal prolapse have been associated with
erythromycin in swine. Intravenous injections must be given very slowly,
as the intravenous forms can readily cause thrombophlebitis. Allergic
reactions can occur, but are thought to be very rare.

Oral erythromycin
should not be used in ruminants as severe diarrheas may result. In foals
treated with erythromycin, a mild, self-limiting diarrhea may occasionally
occur. Adult horses may develop severe, sometimes fatal diarrheas from
erythromycin and the use of the drug in adults is very controversial.

Erythromycin may alter
temperature homeostasis in foals. Foals between the ages of 2 and 4 months
old have been reported to develop hyperthermia with associated respiratory
distress and tachypnea. Physically cooling off these animals is reported
to be successful in controlling this effect.

Overdosage/Acute
Toxicity -
With the exception of the adverse effects outlined above, erythromycin is
apparently quite non-toxic. However, shock reactions have been reported in
baby pigs receiving erythromycin overdosages.

Drug Interactions
- Because erythromycin, the lincosamides (clindamycin,
lincomycin), and chloramphenicol all bind to the 50S ribosomal
subunit, competition for binding can occur and some clinicians state these
drugs should not be used concurrently. In vitro synergy with other
antimicrobials (e.g., sulfonamides, rifampin) has been reported
with erythromycin. The concomitant use of erythromycin with bactericidal
antibiotics (e.g., penicillin) is controversial, but documentation
of either clinical synergy, additive activity, or antagonism is apparently
lacking.

Decreased clearance of
theophylline may occur with resultant toxicity in patients
receiving erythromycin (particularly high dosages). Patients should be
monitored for symptoms of theophylline toxicity and serum theophylline
levels monitored if necessary.

Patients stabilized on
warfarin anticoagulant therapy may develop prolonged prothrombin
times and bleeding when erythromycin is added. Enhanced monitoring is
recom­mended.

The metabolism of
methylprednisolone may be inhibited by concurrent administration of
erythromycin. The clinical significance of this interaction is unknown.
Erythromycin may increase the bioavailability of digoxin in a small
percentage of human patients and can lead to digoxin toxicity. Veterinary
significance of this interaction is questionable. Interactions have also
been reported with erythromycin and the following human drugs (rarely used
in veterinary species—refer to other references if necessary):
carbamazepine, cyclosporine (systemic), and triazolam.

Client Information
- The intramuscular 100 mg/ml (Erythro-100®)
& 200 mg/ml prod­ucts (Erythro-200®)
have quite specific instructions on where and how to inject the drug.
Refer to the label directions or package insert for more information
before using.

Erythro®-Dry (Rhone Merieux);
(OTC) Approved for use in dry dairy cattle. Milk withdrawal = 36 hours.
Slaughter withdrawal = 14 days nor within 96 hours of calving. Calves born
to treated cows may not be slaughtered for food at less than 10 days of
age.

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